| Autor: |
S, Stephens, S, Emtage, O, Vetterlein, L, Chaplin, C, Bebbington, A, Nesbitt, M, Sopwith, D, Athwal, C, Novak, M, Bodmer |
| Rok vydání: |
1995 |
| Předmět: |
|
| Zdroj: |
Immunology. 85(4) |
| ISSN: |
0019-2805 |
| Popis: |
A murine antibody to human tumour necrosis factor-alpha (TNF-alpha) (CB0010) was complementarity-determining region (CDR)-grafted using human IgG4 heavy and kappa light chain constant regions. In cynomolgus monkeys, the grafted antibody (CDP571) was eliminated with a half-life of 40-90 hr, two to three times longer than CB0010, and immunogenicity was reduced by > 90%. Responses to the constant regions were almost entirely eliminated and responses to the CDR loop (anti-idiotype) were lowered. CDP571 was given to 24 human volunteers in doses from 0.1 to 10.0 mg/kg. It was well tolerated, with a half-life of approximately 13 days. Anti-CDP571 antibodies were low or undetectable at higher doses. At lower doses, anti-CDP571 peaked at 2 weeks and then declined. The response was primarily IgM (in contrast to the cynomolgus monkey, where by 5 weeks IgG predominated) and was against a conformational epitope comprising heavy and light chain CDR loops. No antibodies were detected against the gamma 4/kappa domains or frameworks. The response had little or no effect on CDP571 binding to TNF-alpha or on plasma clearance. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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